Molded pick for handling biopsy specimens

ABSTRACT

A molded pick for handling biopsy specimens which includes an elongated shaft having a tapered blunt short barb at one end and a forked device at the opposite end of the shaft, the forked device having a blunt spatula prong as one fork and a sharp tapered point as the other fork.

This application is a division of application Ser. No. 08/392,670, filedMar. 23, 1995, now U.S. Pat. No. 5,593,851, which is a File WrapperContinuation of Ser. No. 08/221,311 filed Apr. 1, 1994 now abandon.

The present invention relates to a test kit for use in the rapiddiagnosis of gastric disease by the detection of Helicobacter pyloribacteria in a gastric biopsy specimen. The test kit includes means forhandling a biopsy specimen and a test composition containing urea and acombination of dye indicators as described in my co-pending U.S. patentapplication, Ser. No. 08/195,954 filed Feb. 14, 1994; the entiredisclosure of said application being incorporated herein by reference.

It has become well-established that (1) the bacteria Helicobacter pyloricauses chronic active gastritis (see the annexed Bibliography for thenumbered references), and that (2) virtually all patients suffering fromduodenal ulcer and perhaps 80% of patients having gastric ulcers areinfected by H. pylori. There is also epidemiological evidence that (3)correlates the presence of H. pylori with gastric cancer. In view ofthese facts, a test for the presence of H. pylori in a gastric biopsyspecimen has become the preferred method for the diagnosis of gastricdisease.

The purpose of the present invention is to provide an improved test kitfor the rapid, convenient, reliable and accurate detection of H. pyloriin gastric biopsy tissue.

BACKGROUND AND PRIOR ART

An extensive description of the background and prior art for thediagnosis of gastric disease by the detection of H. pylori in gastrictissue is set forth in my co-pending U.S. patent application Ser. No.08/195,954 and is incorporated herein above by reference.

Briefly, it having been seen that the bacteria H. pylori is present inendoscopically obtained gastric biopsy specimens from both gastric andduodenal ulcer patients and it being known that the enzyme urease isalways associated with that bacteria, the concept of diagnosing thepresence of such ulcers by testing biopsy specimens for urease suggesteditself. Chemical tests for urease were already known in the art. In onesuch test a urea-containing broth provides a positive urease reaction(hydrolysis of urea) as below:

    urea+H.sub.2 O urease→NH.sub.3 +CO.sub.2

as indicated by a change in color of the indicator Bacto phenol red fromyellow (pH 6.8) to red to cerise at pH 8.1 or more alkaline due to theproduction of ammonia an&or ammonium carbonate by the urea-ureasereaction. See the Difco Manual, 9th edition, Difco Laboratories,Detroit, Mich., (1953). The urea broth described in the Difco Manual wasapparently used by B. J. Marshall in the work described in the RapidDiagnosis of Campylobacteria associated with Gastritis, The Lancet, Jun.22, 1985.

This type of urease test has come into commercial clinical use. In theUnited States a commercial test product is marketed under the trademark"CLOtest®". This product is described in U.S. Pat. No. 4,748,113 issuedto Barry J. Marshall on May 31, 1988. The test of the Marshall patentcommercially employs urea, a buffer, a bactericide, arid phenol red asthe dye indicator. This test is carded out in an alkaline pH rangeshowing a positive result on a change of the indicator from yellow tored at a pH in the range from about 6.8 to 9.

In the Marshall test, a gastric mucosal biopsy specimen containing H.pylori is placed in solution or an aqueous agar gel containing urea, andindictor, phenol red, and buffers. The urease in H. pylori converts tourea to ammonia which raises the pH and turns the agar color from ayellow to red, indicating a positive test. According to the packageinsert in the Marshall commercial phenol red test (CLOtest®)it isrecommended that the test be incubated at 30°-40° C for three hours andit is indicated that it may take up to 24 hours to develop a positivetest. This test relies on the passive diffusion of urease from the cellwall of the bacterium into the agar gel testing solution. Moreover,operating as it does at a pH above 6.5, the test may give a positiveresult with bacteria other than H. pylori and thus is not entirelyspecific for Helicobacter pylori. Specifically, Proteus, Pseudomonas,and E. Coli species may cause a color change at this level and give afalse positive test.

Another test kit for H. pylori is available commercially from SerimResearch Corporation, 1000 Randolph St., Bldg. 17, c/o Miles Inc.,Elkhart, Ind. 56515 under the trademark "PyloriTek". This kit includestest strips having a substrate pad containing 3.3% urea and, in aseparate matrix, a reaction pad containing 0.1% bromophenol blue dyeindicator and 0.2% sulfamic acid. The test kit also contains, in aseparate container, a hydration solution consisting of 1.8% Tris buffer.This kit, makes use of the same urease-urea reaction as the Marshalltest to produce gaseous ammonia which changes the bromophenol blue fromits original yellow color to make a blue test spot over a biopsyspecimen on a yellow field to indicate a positive test. This test issaid to be readable in 120 minutes and should not be read after thattime to avoid false positives. While the two-hour usual test time is animprovement, it is apparent that an even more rapid and less complicatedtest would be desirable.

SUMMARY OF THE INVENTION

The present invention resides in the provision of a compact test kit fordetecting H. pylori. in a gastric biopsy specimen which comprises aclosed well or reaction vessel containing a gelled test composition,means for exposing the well, and means for introducing the biopsyspecimen to the gelled test composition in the well. The kit may also beprovided with means to record pertinent data as to the patient'sidentity and the time and date of the test. The kit may also includemeans to seal the well after use. The kit may also be provided with acolor spectrum for determining the results of the test by comparisonwith the color change of a combination of dye indicators in the testcomposition. The test composition is disclosed in detail in myco-pending U.S. patent application Ser. No. 08/195,954 referred toabove.

DETAILED DESCRIPTION OF THE INVENTION

The invention will now be described in greater detail in conjunctionwith the accompanying drawings, in which:

FIG. 1 is a top plan view of a preferred test kit;

FIG. 2 is a bottom plan view of the test kit of FIG. 1;

FIG. 3 is another bottom plan view of the test kit of FIGS. 1 and 2,showing a peelable label partially stripped away to uncover agel-containing well in the test kit, and also showing the operation ofmeans for removal of a biopsy pick from the test kit;

FIGS. 4 and 5 are detail drawings on an enlarged scale showing the meansfor removal of the biopsy pick from the test kit of FIGS. 1, 2 and 3;

FIG. 6 is a bottom plan view of the test kit of FIGS. 1-5 showing theuse of the biopsy pick in placing a biopsy specimen in the gel in thetest well;

FIG. 7 shows the use of the forked end of the biopsy pick inmanipulating the biopsy specimen in the test well; and

FIG. 8 shows the peelable label resealing the well in the test kit afterinsertion of the biopsy specimen.

Referring now to the accompanying drawings, a preferred test kit of theinvention 10 has a body member 12 including an upwardly open traydivided into two compartments 14 and 16 by a longitudinally extendingupright partition wall 18. Two outer edges of the larger opencompartment 14 are closed by upstanding walls 20 and 22. Upstandingpartition 18 closes a third inner side of compartment 14, the fourthside of compartment 14 being open at 24. The larger compartment 14 ofthe tray in the test kit contains a well 26 integral with the base 30 ofthe compartment 14. The well 26 is open at 28 through base 30 ofcompartment 14 but is closed on its four sides and the bottom 32 whichis upward in FIG. 1 and downward in FIG. 2. The well 26 is preferablytransparent although it is only necessary that it be open at 28 to makeits contents visible.

The well 26 is filled with a test composition 32 containing urea and adye indictor which changes color when a gastric biopsy specimencontaining Helicobacter pylori is placed in the well. The well 26containing the test composition 32 is closed at its open side 28 by apeelable sealing means 34 which extends over an indentation 62 in theopen end 24 of compartment 14. The peelable sealing means 34 is peelablyadhered to the back of lower surface 30 of the compartment 14.

A means for handling a biopsy specimen is removably mounted in thesecond longitudinal compartment 16 which is upwardly and downwardly openas shown in FIGS. 1, 2 and 3. The means for handling the biopsy specimenis preferably a pick 36 having an elongated shaft 38 having a sharppoint or bifurcated point 40 at one end and a forked 42 device at theother end including a sharp point 44 and a blunt prong 46.

The means for handling a biopsy specimen: such as the pick 36 isremovably mounted in the compartment 16 by any suitable means such as byan adhesive or by a frangible integral molded joint. In the preferredembodiment shown in FIGS. 1, 2 and 3, the pick 36 is integrally butfrangibly molded with a boss 48 which is firmly molded with or mountedon the wall 18 and extending into the compartment 16. The longitudinalcompartment 16 containing the pick 36 has a deformable outer wall 50which may optionally have a boss 52 extending into compartment 16adjacent to or in contact with the pick 36. The pick 36 preferably hasan enlargement 54 at the center of its shaft 38 intermediate the boss 48and boss 52. The pick 36 is broken away from its frangible connectionwith boss 48 by deformation of the wall 50, by thumb pressure of theuser or otherwise, to press the wall 50 inwardly to force the boss 52into contact with the enlarged portion 54 of the pick to break it awayfrom its frangible mounting on the boss 48.

An especially preferred embodiment of the means for mounting anddemounting the pick is shown in FIGS. 4 and 5 in which the preferredconfiguration of the boss 48 extends outwardly from the inner wall 18 ofthe compartment 16 and has an upper planar side 56 and a lower slantingside 58 and a generally triangular cross section. The central enlargedportion 54 of the pick is frangibly connected to the under side of thelower slanting edge 58 of the flange 48. As the wall 50 is deformedinwardly by thumb pressure as shown in FIG. 3, the enlarged portion 54of the pink is forced against the slanted surface 58 of the boss 48until the connection is broken between the pick and flange and the pickis freed from its mounting.

Having freed the pick 36, it may be used as shown in FIGS. 7 and 8 topick up the biopsy specimen by the point 40 as in FIG. 6 and to force itinto the test composition 32 in the well 26. As shown in FIG. 7, theforked end 42 of the pick 36 may be used to position and firm the biopsyspecimen in the test composition using either or both of the sharp point44 or blunt prong 46 of the forked end of the pick.

FIG. 8 shows the use of the peelable sealing means 34 to re-seal thewell 26 after insertion of the biopsy specimen. This peelable sealingmeans may also serve as a label to record the identity of the patient,the time and date of the test as shown in FIG. 8.

As shown in FIG. 1, the other side of the peelable sealing means 34preferably carries a spectrum of colors and designations of the pH andnegative (e.g. light green), slightly positive (e.g. medium green),moderately positive (e.g. dark green), and markedly positive responses(e.g. very dark green or blue), to this test. Other information andinstructions may also be shown on this peelable label which can be readthrough the preferably transparent surface of the bottom wall 30 ofcompartment 14.

Other embodiments of the invention will be apparent from the preferredembodiments described above.

What is claimed is:
 1. A molded pick for handling a biopsy specimen,comprising:an elongated shaft havinga tapered blunt short barb at oneend, and, a forked device at the opposite end of said shaft, said forkeddevice having a blunt, spatula prong as one fork and a sharp taperedpoint as the other fork.
 2. A molded plastic pick of claim 1 having anelongated boss intermediate the ends of said shaft for frangiblymounting said pick in a kit for testing gastric biopsy specimens.